Sperm Seem to Sense What You Eat

Abstract

Obesity affects the epigenome of a man’s sperm, according to a new study. The study compares sperm from obese and lean men, and from men before and after undergoing bariatric surgery. Previous studies in rodents have suggested that a father’s metabolic state can affect the health of offspring, and epidemiological studies in humans have hinted at a similar effect. But the mechanisms behind such apparent effects have been difficult to tease out. Previous studies in flies and worms have suggested that piRNAs play a role in transgenerational inheritance, and other studies in various organisms hint at a role for DNA methylation. These data led Ida Donkin et al. [1] to examine small RNAs and DNA methylation in the sperm of lean and obese men. These researchers found that 37 piRNAs appeared to have distinct expression levels in the two groups, and one of the piRNAs seems to target a known regulator of food intake, which may give it the ability to regulate a suite of genes. The researchers also saw that a large number of genes—about 9,000—were differentially methylated between lean and obese men, though for many of them the effect was fairly small. Their analysis hinted that some of these genes may be involved in metabolism and central nervous system function. Curiously, many of the affected genes overlapped with a dataset obtained from an analysis of men whose offspring had Autism Spectrum Disorder. The findings are also intriguing in light of a recent study suggesting that genes involved in neurological disorders and metabolism escape DNA demethylation in human primordial germ cells. The researchers similarly observed distinct DNA methylation profiles in men before and after they had undergone bariatric surgery— although the profile of affected genes did not match with the lean and obese men, there was some overlap. Whether DNA methylation is a mechanism for transgenerational inheritance or not remains an active area of investigation, and other studies examining the effects of metabolism on sperm are ongoing. For instance, another recent study, by Jeremy Shea et al. [2], provides evidence that DNA methylation in sperm is not directly involved in dietary reprogramming of offspring metabolism in mice.